The present invention relates to automatical introduction of reference fluid in apparatus for analysis of physiological fluids.
A known apparatus of this type is an apparatus for blood gas analysis. Such apparatus are by way of example used in hospitals and medical laboratories where they are permanently ready for operation with a view to analysis of blood samples immediately after their being taken. The apparatus analyses the blood samples for example by measuring partial pressure of CO2 (pCO2), partial pressure of O2 (pO2) and pH. In order that an apparatus works in a reliable way, i.e. provides reliable measuring results, it must normally be calibrated at appropriate intervals. Furthermore, the calibration must be controlled frequently. Therefore, a quality control procedure is, among other, performed where the apparatus analyses a control solution with known values for at least some of the parameters which the apparatus is adapted to measure. According to guidelines from National Committee for Clinical Laboratory Standards (NCCLS DOCUMENT C27-A, Vol. 13, No. 6) for collection and handling an arterial specimen for pH and blood gas analysis and for calibrating the analyzer together with recommendations for an acceptable quality control program, it is recommended to perform said quality control program once per shift (i.e. three times a day by treble shift) such that three different levels (high, middle and low) for the parameters to be controlled are measured in three consecutive shifts.
So far this quality control has been performed manually in the way that an operator injects or introduces a control solution with specific contents in the analysis apparatus according to a fixed schedule, and the apparatus then carries out a control program. The result of this control is printed and if the measured values of the parameters in question lie within predetermined limits, the control is accepted, and the apparatus may be used. Otherwise it may be necessary to calibrate the apparatus before it is used for analysis of a sample. The control program is terminated by a rinse program by which the apparatus rinses itself of control solution.
The control solution is usually supplied in small containers or ampoules, the contents of one ampoule being used for one quality control. The ampoules are usually designed as ampoules with a breakable neck. Larger containers for several controls are also known. The containers for control solutions are described in the literature since the beginning of the 1970s. One of the latest publications on containers with control solutions is U.S. Pat. No. 5,230,427.
The ampoule contains both a liquid phase and a gas phase, a temperature dependent balance being between dissolved gas in the liquid phase and gas in the gas phase. In order to know the exact contents of a given gas in the solution, it is therefore necessary that the temperature of the solution in the ampoule is known, and that this temperature is uniform within the entire volume of the ampoule. In order to ensure a uniform temperature distribution, the ampoule is shaked prior to the quality control. Alternatively, it may be ensured that the ampoule has been kept at a constant known temperature for some time.
A problem with the prior art technology of manual quality control is that in the nature of the case, it requires qualified personnel efforts as there are some (human) error possibilities, for instance that a quality control is forgotten or that the quality control procedure is carried through incorrectly.
It is the object of the invention to avoid or reduce the drawbacks of the prior art.
According to the invention, an apparatus for analysis of physiological fluids, such as an apparatus for blood gas analysis, is characterized by equipment for automatic introduction of reference fluid for the apparatus, which equipment comprises a holder for concurrent hold of several sealed containers with reference fluid, means for bringing a selected container and means for opening the container into a specific position in relation to each other, means for bringing the opened container and an inlet aggregate for introduction of fluid from the container into the apparatus into a specific position in relation to each other, means for activating the inlet aggregate, means for removing the container and the inlet aggregate from each other, and programmable control means for control of the introduction of reference fluid into the apparatus.
The holder may be a detachable or non-detachable part of the apparatus. Further, the holder may comprise a device into which the sealed containers may be loaded individually or it may comprise a support means adapted for removably holding or being attached to a magazine wherein several sealed containers are concurrently held.
The control means of the device then ensures the introduction of reference fluid at pre-programmed times, the control means selecting a container with a specific reference fluid and the device then automatically ensures that the container is opened, its contents introduced into the apparatus and the container and the inlet aggregate removed from each other.
In a preferred embodiment, the inlet aggregate is constituted by the inlet aggregate of the apparatus for fluid samples for analysis. Thereby is avoided a separate aggregate for transmission of the fluid from the container to the inlet aggregate of the apparatus for fluid samples to be analysed, such as blood samples.
The apparatus according to the invention may be designed in a particularly simple way if the means for bringing a selected container and the inlet aggregate into a specific position in relation each other comprise means for moving a magazine and/or the holder of the sealed containers. The means for moving the magazine and/or the holder may further be adapted to agitate the containers such that a shaking effect is obtained.
The means for bringing a selected container and the means for opening the container into a specific position in relation to each other and the means for bringing the opened container and an inlet aggregate for introduction of fluid from the container into the apparatus into a specific position in relation to each other may be constituted by the same means. Furthermore, said positions of the container in relation to means for opening the container and in relation to an inlet aggregate for introduction of fluid from the container into the apparatus may be one and the same position.
Preferably, the means for opening the container comprise an element which is made to press against an opening area on the container which is thus opened.
In all aspects of the invention, the sealed containers with reference fluid may or may not contain both a liquid phase and a gas phase, two phases being preferred.
According to the invention, there is further provided a unit to be mounted into and to be a part of an apparatus for analysis of physiological fluids, which unit is characterized in a holder for concurrent hold of several sealed containers with reference fluid, means for bringing a selected container and means for opening the container into a specific position in relation to each other, means for bringing the opened container and an inlet aggregate for introduction of fluid from the container into the apparatus into a specific position in relation to each other, and means for removing the container and the inlet aggregate from each other. When mounted, this unit forms an integrated part of an apparatus according to the invention as described above.
According to the invention, there is further provided an ampoule containing a reference fluid and comprising a body with an opening area having an opening the circumferential edge of which lies in one and the same plane, said body being hermetically sealed by a membrane mounted to the circumferential opening edge of the body, said ampoule being characteristic in that the membrane is planar and comprises a layer of a glass material. The membrane may consist of one or several layers of glass or the membrane may comprise at least one layer of glass and at least one layer of a polymeric material. The glass material is preferably a borosilicate glass or a silicon or aluminum oxide. However, other types of glasses may be useful as well.
In the sealed ampoule the membrane may show some distortion from planar as a result of the sealing process. However, the membrane must be planar prior to the sealing process. When referring to the circumferential edge as lying in one and the same plane it has to be understood that sectional views of the circumferential edge may show any suitable linear or non-linear shape.
This ampoule may be manufactured reproducibly with a very thin (30-150 xcexcm) and thus easily breakable membrane. Furthermore, the membrane provides the ampoule with an opening area which has a uniform thickness. Thus, the ampoule according to the invention is advantageous as compared to the well-known glass ampoules with breakable necks, these ampoules having a wall thickness of 0.5-1 mm. It has been attempted to manufacture these prior art ampoules with thin bottoms in order to use the bottom as an opening area to be broken immediately before the withdrawal of reference fluid from the ampoules. However, is has shown very difficult to produce the prior art ampoules with a uniform and reproducible thickness of the bottom. Further, these prior art ampoules turned out not to be sturdy, but did often break during transportation.
The ampoule according to the invention is also advantageous as compared to the ampoules disclosed in the above mentioned U.S. Pat. No. 5,230,427. The ampoules disclosed therein comprises a body with an opening sealed by a membrane of a polymeric layer and a metal layer. These prior art ampoules suffer from the drawback that the metal layer is exposed to corrosion and that any oxygen contained in the reference fluid may diffuse through the polymeric layer into the metal layer, thereby causing corrosion. An embodiment of these prior art ampoules are commercially available under the trade name StatPal(copyright)II, Calibration Kit, from PPG Industries, Inc., La Jolla, Calif., USA. These ampoules suffer from the drawback that they have to be kept individually in bags with a controlled atmosphere in order to maintain the composition of the reference fluid as required during storage.
Further according to the invention, there is provided another ampoule containing reference fluid and comprising a body with an opening area having an opening sealed with a membrane, which ampoule is characterized in that the opening area comprises a cap which has a penetration part provided with a through hole, which penetration part is arranged for breaking through the membrane in order to open the ampoule by movements against the body. The body is preferably oblong and the opening area is preferably placed in one end of the body. Such an ampoule is particularly suitable for use in connection with an apparatus according to the invention, thus permitting to lead a pipe through the hollow penetration part and down into the container in order to aspirate fluid for the apparatus. This tube is preferably a part of the inlet aggregate.
According to the invention, there is further provided a magazine comprising several ampoules with reference fluid for an apparatus for analysis of physiological fluids, such as an apparatus for blood gas analysis, reference fluid with predetermined content being provided in different ampoules, which magazine is arranged for loading as a unit to an apparatus of said type. Different ampoules may have different predetermined contents and the reference fluid in the ampoules may be a control solution for quality control of the apparatus. By such a magazine, the operation of an apparatus according to invention is particularly simple as the concurrent hold of several sealed containers with reference fluid by the holder, may be achieved merely by loading or attaching a new magazine.